title: Methanolysis of triterpenoid saponin from Ardisia gigantifolia stapf. and structure-activity relationship study against cancer cells.
abstract: Thirteen 13,28-epoxy triterpenoid saponins were isolated from Ardisia gigantifolia stapf. and one potential anti-tumor saponin was methanolysised by H2SO4 to afford four new compounds. The seventeen compounds were evaluated for their anti-proliferative activity on A549, HCT-8 and Bel-7402 cells. The structure-activity relationship analysis indicated that the incorporation of =O group at C-16, L-rhamnose at R(5) and acetyl group at OH-6 of the D-glucose lead to a significant increase of the cytotoxic activity on A549 and HCT-8 but significant reduction of the cytotoxic activity on Bel-7402 cells. The synthesized saponins losing 13,28-epoxy and CHO at C-30, losed their cytotoxicities on A549 and HCT-8 cells, suggesting that the two moieties play an essential role for activity. 3β-O-α-L-rhamnopyranosyl-(1→3)-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-l-arabinopyranoside-16α-hydroxy-13,28-epoxy-oleanane (2) showed better inhibitory activity to Bel-7402 (IC50 0.86 μM) than that of 5-FU (IC50 8.30 μM), which indicate that five saccharide and methyl moiety at C-30 are important for anti-proliferative activity. The activities of saponins 15>14, 17>16, suggested that the configuration of 28,30-epoxy is preferable to be 30(R) rather than 30(S) on Bel-7402 cells. Further molecular mechanism studies of saponins 1 and 2 were carried out on the cell cycle distribution of Bel-7402 cells.
authors.affiliation: Department of Clinical Pharmacology, General Hospital of PLA, Beijing 100853, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Mu
authors.forename: Cui-Li
authors.initials: CL
authors.lastname: Huang
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Zhou
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Guo
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D031644:Ardisia / Q000737:chemistry*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D012503:Saponins; D014315:Triterpenes; D000432:Methanol
keywords: Ardisia gigantifolia; Methanolysis; Structure–activity relationship; Triterpenoid saponins